Abstract
While the association between metformin and mortality in obesity-related cancers (ORC: breast (BrCa), colorectal (CRC), endometrial (ECa), and ovarian (OCa)) remains inconsistent, the impact of weight loss medication (WLM) on mortality in ORC is largely unexplored, particularly among older women. This study aims to investigate the association between pre-diagnostic use of metformin and WLM with all-cause and cancer-specific mortality in older women with ORC. A retrospective cohort of 63,907 women (≥ 65 years) with ORC was identified using SEER-Medicare 2007-2015 data. Pre-diagnostic prescriptions of metformin and WLM were ascertained, and inverse probability of treatment weighting using propensity score (IPTW-PS) was utilized to balance baseline patient characteristics. Cox proportional hazards and competing-risks models were conducted. Metformin was associated with all-cause- (HR:1.86; 95% CI: 1.81-1.92) and ORC-specific mortality (HR: 1.71; 95% CI: 1.63-1.77). Likewise, WLM was associated with all-cause- (HR:1.64; 95% CI: 1.59-1.71) and ORC-specific mortality (HR: 1.55; 95% CI: 1.48-1.62). Dual use of metformin and WLM was associated with all-cause- (HR:1.39; 95% CI: 1.34-1.45) and ORC-specific mortality (HR: 1.28; 95% CI: 1.21-1.53). Significant associations were observed in ORC subgroup analyses, except that WLM was inversely associated with ECa-specific morality. Pre-diagnostic metformin and WLM were associated with an increased mortality risk in older women with ORC, with effects more pronounced among metformin users. Further prospective studies are needed to substantiate these findings.